10.3389/fnins.2018.00075.s001
Magdalena Dabrowska
Magdalena
Dabrowska
Wojciech Juzwa
Wojciech
Juzwa
Wlodzimierz J. Krzyzosiak
Wlodzimierz
J. Krzyzosiak
Marta Olejniczak
Marta
Olejniczak
DataSheet1.pdf
Frontiers
2018
genome editing
CRISPR/Cas9
neurodegenerative diseases
repeat expansion
engineered nucleases
Huntington's disease
nonsense-mediated decay
2018-02-26 10:00:20
Dataset
https://frontiersin.figshare.com/articles/dataset/DataSheet1_pdf/5924653
<p>Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in the first exon of the huntingtin gene (HTT). The accumulation of polyglutamine-rich huntingtin proteins affects various cellular functions and causes selective degeneration of neurons in the striatum. Therapeutic strategies used to date to silence the expression of mutant HTT include antisense oligonucleotides, RNA interference-based approaches and, recently, genome editing with the CRISPR/Cas9 system. Here, we demonstrate that the CAG repeat tract can be precisely excised from the HTT gene with the use of the paired Cas9 nickase strategy. As a model, we used HD patient-derived fibroblasts with varied numbers of CAG repeats. The repeat excision inactivated the HTT gene and abrogated huntingtin synthesis in a CAG repeat length-independent manner. Because Cas9 nickases are known to be safe and specific, our approach provides an attractive treatment tool for HD that can be extended to other polyQ disorders.</p>